Darunavir/cobicistat showing similar effectiveness as darunavir/ritonavir monotherapy despite lower trough concentrations:

Abstract

Introduction: When darunavir (DRV) 800 mg is boosted with 150 mg cobicistat (DRV cobi ), DRV trough concentration (C trough ) is about 30% lower as compared to 100 mg ritonavir (DRV rtv ). DRV cobi shows similar virological efficacy as DRV rtv when combined with two nucleos(t)ide analogue reverse-transcriptase inhibitors, but it is unknown whether a lower DRV C trough would undermine the effectiveness of DRV cobi when given as monotherapy (mtDRV cobi ). Methods: Prospective observational study on virologically suppressed HIV-infected subjects who switched to mtDRV cobi . Virological failure was defined as two consecutive HIV-RNA >200 copies/mL. Efficacy was evaluated by intention-to-treat (ITT) and on-treatment (OT) analyses, and compared with data from a previous cohort of subjects on mtDRV rtv conducted at our centre. Plasma DRV C trough was measured using LC-MS/MS. Results: A total of 234 subjects were enrolled. At week 96, the efficacy rates were 67.8% (CI 95 , 61.8 to 73.7) by ITT and 86.9% (CI 95 , 78.0 to 87.7) by OT analyses. The corresponding rates in our historical DRV rtv controls were 67.6% (CI 95 , 60.0 to 75.2) and 83.6% (CI 95 : 77.2 to 90.0). A total of 135 DRV determinations were performed in 83 subjects throughout the follow-up period, with a median plasma DRV C trough of 1305 ng/mL (range, 150 to 5895) compared with 1710 ng/mL (range, 200 to 3838) in subjects on monotherapy with DRV rtv (p = 0.05). Conclusions: DRV C trough was lower in HIV-infected subjects receiving DRV cobi than with DRV rtv . However, this did not appear to influence the efficacy of DRV cobi , when administered as monotherapy.